Khozyainova, A. | Search bioRxiv

bioRxiv2025

Single-cell transcriptomics reveals a conserved embryonic progenitor in different human cancers

Cellular plasticity, a critical feature of embryonic development, is often reactivated in cancer, enabling tumor cells to acquire stem-like properties and facilitate uncontrolled growth. This study compares cellular plasticity in cancer and early human development by integrating single-cell data from three cancers and embryoid bodies. The analysis identifies a shared, highly proliferative progenitor-like state, driven by an E2F-TFDP transcriptional axis and enriched in key cell-cycle regulators UBE2C, TOP2A, BIRC5, and NUSAP1. Functionally linked to cell-cycle progression and DNA repair, this state acts as a lineage hub within tumors. Spatial transcriptomics revealed that this state is enriched in lung adenocarcinoma and in lung tissue with basal cell hyperplasia, a potential precursor to squamous cell carcinoma. Validation across eight cancer types demonstrates a prevalence of this program in tumors versus normal cells. Collectively, these findings define a conserved mechanism of tumor plasticity with potential for early detection and targeted therapy. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=150 SRC="FIGDIR/small/693590v2_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@d8d8fborg.highwire.dtl.DTLVardef@8d5cb7org.highwire.dtl.DTLVardef@c1f3b0org.highwire.dtl.DTLVardef@165af61_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2023

Revealing Molecular Mechanisms of Early-Onset Tongue Cancer by Spatial Transcriptomics

Tongue cancer at a young age demonstrates an increase in incidence, aggressiveness, and poor response to therapy. Classic etiological factors for head and neck tumors such as tobacco, alcohol, and human papillomavirus are not related to early-onset tongue cancer. Mechanisms of development and progression of this cancer remain unclear. In this study, we performed spatial whole-transcriptome profiling of tongue cancer in young adults compared with elderly patients. Oxidative stress, vascular mimicry, and MAPK and JAK-STAT pathways were enriched in early-onset tongue cancer. Tumor microenvironment demonstrated increased gene signatures corresponding to myeloid-derived suppressor cells, tumor-associated macrophages, and plasma cells. The invasive front was accompanied by vascular mimicry with arrangement of tumor-associated macrophages and aggregations of plasma cells and lymphocytes organized into tertiary lymphoid structures. Taken together, these results indicate that early-onset tongue cancer has distinct spatial transcriptomic features and molecular mechanisms compared to older patients. HIGHLIGHTSO_LIEarly-onset tongue cancer demonstrates extremely downregulated oxidative phosphorylation and upregulated glycolysis. C_LIO_LIMAPK pathway is the key player in the pathogenesis of tongue cancer in young adults. C_LIO_LIEarly-onset tongue cancer is characterized by JAK-STAT dependent vascular mimicry supported by tumor-associated macrophages at the invasive edge. C_LIO_LITongue cancer microenvironment in young adults enriches for immunosuppressive myeloid derived suppressor cells and demonstrates reduced antigen presentation function. C_LIO_LIThe tumor border in early-onset tongue cancer is enriched with plasma cells and lymphocytes in tertiary lymphoid structures. C_LI

cancer biology↗